{"title":"Krill Oil Mitigates Cisplatin-Induced Ovarian Toxicity via Attenuation of Oxidative Stress and Inflammatory Pathways.","authors":"Erson Aksu, Oytun Erbas","doi":"10.3390/cimb47090708","DOIUrl":"10.3390/cimb47090708","url":null,"abstract":"<p><p>Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation against cisplatin-induced ovarian damage in a rat model, with a focus on oxidative stress, inflammation, follicular dynamics, and stromal fibrosis. Twenty-one adult female Wistar albino rats were randomized into three groups: control, cisplatin-treated, and cisplatin + krill oil-treated. Ovarian toxicity was induced via intraperitoneal injection of cisplatin (2.5 mg/kg, twice weekly for four weeks). Krill oil (4 mL/kg/day) was administered orally during the same period. Ovarian histopathology, follicle counts (primordial, primary, secondary, tertiary), stromal fibrosis, and biochemical markers, including plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and ovarian levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Toll-like receptor 4 (TLR4), TNF-α, NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-1β were evaluated. Cisplatin significantly reduced primordial, primary, secondary, and tertiary follicle counts while increasing stromal fibrosis (<i>p</i> < 0.001). Krill oil co-treatment notably ameliorated follicular depletion-improving follicle counts by 38.16%, 54.74%, 62.5%, 40.43%, respectively-and reduced fibrosis (<i>p</i> = 0.017). Biochemically, cisplatin decreased AMH levels and Nrf2 expression while elevating MDA, TNF-α, TLR4, NLRP3, and IL-1β levels (<i>p</i> < 0.001). Krill oil supplementation restored AMH (<i>p</i> = 0.002) and Nrf2 (<i>p</i> = 0.003) levels, while reducing MDA (<i>p</i> = 0.009), NLRP3 (<i>p</i> < 0.001), ovarian IL-1β (<i>p</i> = 0.005), plasma IL-1β (<i>p</i> < 0.001), TLR4 (<i>p</i> = 0.001), plasma TNF-α (<i>p</i> = 0.001), and ovarian TNF-α (<i>p</i> < 0.001), compared to the cisplatin group. Krill oil exerts significant antioxidant and anti-inflammatory effects, offering a promising strategy to mitigate cisplatin-induced ovarian damage and preserve fertility in young cancer patients.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KMO Inhibition Improves Seizures and Depressive-like Behaviors Without Aggravating Cognitive Impairment in Epileptic Mice.","authors":"Jingwen Xu, Yifen Huang, Liping Wei, Ziting Kong, Junling Fu, Lun Cai","doi":"10.3390/cimb47090705","DOIUrl":"10.3390/cimb47090705","url":null,"abstract":"<p><p>The objective of this study is to investigate the effects of kynurenine-3-monooxygenase (KMO) inhibition on seizures, depressive-like behaviors, and cognitive functions in epileptic mice, and to elucidate its impact on the kynurenine metabolic pathway. Male Kunming (KM) mice were randomized into four groups: the epileptic model (EM), epileptic model treated with Ro 61-8048 (RM), healthy control (HC), and healthy control treated with Ro 61-8048 (RC). Chronic epilepsy was induced in the EM and RM groups via an intraperitoneal pilocarpine injection (225 mg/kg). The RM and RC groups received Ro 61-8048 (42 mg/kg). The seizure frequency was monitored continuously using a 24 h video recording. Depressive-like behaviors were assessed with the sucrose preference test (SPT) and forced swim test (FST); cognitive function was evaluated with the Y-maze test and open field test (OFT). The concentrations of kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid (3-HANA) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Compared to the EM group, the RM group exhibited a reduced seizure frequency and severity (<i>p</i> < 0.05), ameliorated depressive-like behaviors (increased sucrose preference in SPT, and decreased immobility time in FST, <i>p</i> < 0.05), and enhanced cognitive performance (elevated spontaneous alternation and reduced non-sequential alternation in a Y-maze, and increased time and distance in a central open field area, <i>p</i> < 0.05). Mechanistically, compared to the RC group, the RM group showed an increased KYNA/KYN ratio, and a decreased 3-HK/KYN ratio (<i>p</i> < 0.05) KMO inhibition rectifies the neurotoxic-neuroprotective imbalance in the kynurenine pathway (downregulating the 3-HK/3-HANA ratio and upregulating the KYNA/KYN ratio), thereby decreasing seizures, depressive-like behaviors, and cognitive deficits. These findings suggest KMO inhibition is a potential therapeutic strategy for epilepsy-associated depression. A further investigation of its mechanisms and clinical applicability is warranted.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Targeted Therapy and Immunotherapy in Metastatic GNET/Clear Cell Sarcoma (CCS) of the Gastrointestinal Tract: A Case Report.","authors":"Raluca Ioana Mihaila, Andreea Veronica Lazescu, Daniela Luminița Zob, Dana Lucia Stanculeanu","doi":"10.3390/cimb47090706","DOIUrl":"10.3390/cimb47090706","url":null,"abstract":"<p><p><b>Background</b>: Gastrointestinal neuroectodermal tumour (GNET), also known as clear cell sarcoma (CCS) of the gastrointestinal tract, is a rare neural crest-derived malignancy characterized by EWSR1-ATF1 or EWSR1-CREB1 fusions. Due to its rarity, there is limited evidence and no established guidelines for standard management. GNET is aggressive, with high rates of local recurrence, metastasis, and mortality. <b>Case Presentation</b>: We report the case of a 46-year-old woman with a family history of gastrointestinal cancers who was diagnosed in 2020 with an intestinal GNET. She underwent a segmental enterectomy as the first step of multimodal therapy. After three years of follow-up, she developed hepatic and peritoneal metastases. In November 2023, she began combined therapy with the anti-VEGF tyrosine kinase inhibitor cabozantinib and the immune checkpoint inhibitor nivolumab. The patient has maintained stable disease for 18 months with good tolerance and no adverse events. Molecular analysis of the tumour, which showed an EWSR1-CREB1 fusion, supported the selection of targeted therapy and immunotherapy as the preferred treatment approach. <b>Conclusions</b>: Immunotherapy and targeted therapy show promise for GNET/CCS treatment, but clinical standards are lacking, and evidence comes primarily from case reports. Additional data are needed to determine the best sequence and combination of therapies for this very rare disease.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandeep R Reddy, Manjunatha Bangeppagari, Sang Joon Lee
{"title":"Immune-Epigenetic Effects of Environmental Pollutants: Mechanisms, Biomarkers, and Transgenerational Impact.","authors":"Sandeep R Reddy, Manjunatha Bangeppagari, Sang Joon Lee","doi":"10.3390/cimb47090703","DOIUrl":"10.3390/cimb47090703","url":null,"abstract":"<p><p>Environmental pollutants such as heavy metals, endocrine-disrupting chemicals, microplastics, and airborne particulates are increasingly recognized for their potential to influence immune function through epigenetic mechanisms. This review examines conserved pollutant-associated pathways at interfaces of immunity and epigenetics, with particular attention to Toll-like receptor-NF-κB signalling, NLRP3 inflammasome activity, and reactive oxygen species-driven cascades. Evidence from cellular, animal, and epidemiological studies indicates that these pathways may converge on chromatin regulators such as DNA methyltransferases, histone deacetylases, and EZH2, leading to DNA methylation shifts, histone modifications, and altered chromatin accessibility. Pollutants are also reported to modulate non-coding RNAs, including miR-21, miR-155, and several lncRNAs, which can act as intermediaries between cytokine signalling and epigenetic remodelling. Findings from transgenerational models suggest that pollutant-linked immune-epigenetic alterations might persist across generations, raising the possibility of long-term consequences for immune and neurodevelopmental health. Comparative analyses further indicate convergence across diverse pollutant classes, pointing to a shared mechanistic axis of immune-epigenetic disruption. Overall, these insights suggest that pollutant-induced immune-epigenetic signatures may contribute to inflammation, altered immune responses, and heritable disease risks, and their clarification could inform biomarker discovery and future precision approaches in immunotoxicology.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome Wide Identification of Sesame Dof Transcription Factors and Functional Analysis of SiDof8, SiDof10 and SiDof34 in Fatty Acid Synthesis.","authors":"Feicui Zhang, Shanyu Chen, Feiling Song, Limin Shi, Xuegao Lv, Zhengmei Zhu, Huabing Lu","doi":"10.3390/cimb47090700","DOIUrl":"10.3390/cimb47090700","url":null,"abstract":"<p><p>The Dof (DNA binding with one finger) protein is one of the unique transcription factors in plants, and it plays an important role in plant growth and stress response. Sesame is an oil-bearing crop with high oil content and rich nutrition. In this study, 34 <i>Dof</i> genes were identified in the sesame genome using bioinformatics technology, and their physicochemical properties, gene structure, conserved motifs, tissue-specific expression and functions in fatty acid synthesis were preliminarily analyzed. The results showed that although there were differences in sequence length, molecular weight and isoelectric point, SiDofs all contained a conservative zinc finger structure, which could be divided into three categories in phylogeny. All 34 <i>SiDof</i> genes contain 1-2 exons, and the conserved motifs among subfamilies are similar. Tissue-specific expression analysis showed that the expression levels of <i>SiDof8</i>, <i>SiDof10</i> and <i>SiDof34</i> were the highest in seeds 24 days after pollination. Overexpression of <i>SiDof8</i>, <i>SiDof10</i> and <i>SiDof34</i> could significantly increase the contents of C18:0, C18:1, C18:2 and C18:3, and all of them are located in the nucleus. There were Dof DNA binding elements in the promoter region of fatty acid synthesis genes. These results provide a theoretical basis for further study on the function of the sesame <i>Dof</i> genes and biological breeding.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of Dietary Exposure to Low-Density Polyethylene Microplastics and Their Potential Role as Estrogen Vectors In Vivo.","authors":"Noura Al-Jandal, Azad Ismail Saheb, Abdulaziz Alkhubaizi, Abrar Akbar, Enas Al-Hasan, Sumaiah Hussain, Hamad Al-Mansour","doi":"10.3390/cimb47090701","DOIUrl":"10.3390/cimb47090701","url":null,"abstract":"<p><p>Microplastics (MPs) are a growing environmental concern due to their ability to adsorb hazardous chemicals, such as estrogens, and be ingested by marine organisms. This study focuses on low-density polyethylene (LDPE), a polymer widely used in Kuwait, to assess its role as a carrier of endocrine-disrupting chemicals (EDCs), specifically estrogens. Biological effects were evaluated using biomarkers such as cytochrome P450 1A (CYP1A) and vitellogenin (Vtg) gene expression. Virgin LDPE MPs were exposed to influent and effluent from a wastewater treatment plant (WWTP) for four weeks to facilitate estrogen absorption. The MPs were then incorporated into fish feed pellets for dietary exposure experiments. Fish were divided into three treatment groups-exposed to either virgin MPs, WWTP-influent MPs, or WWTP-effluent MPs-and monitored over four weeks. The results showed that WWTP-exposed MPs carried detectable levels of estrogen, leading to physiological effects on yellowfin bream. Fish in the control group, which received MP-enriched diets without estrogen, experienced significant weight loss due to nutrient deprivation. In contrast, weight patterns in the treatment groups were influenced by estrogen exposure. The condition factor (CF) decreased across groups during the experiment but remained within acceptable health ranges. A significant reduction in the hepatosomatic index (HSI) was observed in the effluent-exposed group, likely due to lower estrogen levels reducing physiological stress. The findings confirm that LDPE MPs can act as carriers for estrogens, impairing fish growth and metabolism while disrupting biological processes such as cytochrome oxidase function. These results highlight the potential risks of MPs in marine ecosystems and underscore the need for further research to understand their long-term effects.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sublingual Dripping Pill Formulation of <i>Ganoderma amboinense</i> Fruiting Body Extract Attenuates CCl<sub>4</sub>-Induced Liver Fibrosis via Multi-Pathway Regulation.","authors":"Chin-Feng Liu, Chong-Ming Pan, Chun-Lin Lee","doi":"10.3390/cimb47090697","DOIUrl":"10.3390/cimb47090697","url":null,"abstract":"<p><p>Liver fibrosis remains difficult to treat, in part because many hepatoprotective triterpenoids suffer from poor oral bioavailability and lack of optimized delivery formats. <i>Ganoderma amboinense</i> is a rare \"antler\" reishi species long valued in Eastern traditions yet scarcely studied for its phytochemical and pharmacological potential. Here, we report the first investigation of an ethanol-extracted <i>G. amboinense</i> sublingual dripping pill formulation (GDP) in a carbon-tetrachloride (CCl<sub>4</sub>)-induced mouse model of liver fibrosis. Mice treated with GDP at one- and five-times the human equivalent dose were compared to groups receiving unprocessed <i>G. amboinense</i> powder (GP) or purified ganoderic acid A (GA-A). GDP significantly prevented CCl<sub>4</sub>-induced weight loss and hepatomegaly, normalizing liver-to-body weight ratios and serum AST/ALT activities (<i>p</i> < 0.05). Histological evaluation showed that GDP markedly reduced hepatocellular necrosis and collagen deposition, restoring tissue architecture. Furthermore, GDP suppressed hepatic expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, COX-2) and profibrotic markers (TGF-β1, CTGF, α-SMA) to levels comparable with or superior to GA-A. These results demonstrate that a dripping pill dosage form can effectively deliver <i>G. amboinense</i> triterpenoids and unlock their hepatoprotective activity, supporting further development of GDP as a novel liver-support nutraceutical.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long Non-Coding RNAs: Significant Drivers of Carcinogenesis Mechanisms in Head and Neck Squamous Cell Carcinoma.","authors":"Camelia Mia Hotnog, Marinela Bostan, Matei Anghelescu, Viviana Roman, Coralia Bleotu, Razvan Hainarosie, Catalina Voiosu, Stefania Marineata, Ioana-Stefania Bostan, Carmen Cristina Diaconu, Mirela Mihaila","doi":"10.3390/cimb47090698","DOIUrl":"10.3390/cimb47090698","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histone-, Receptor-, and Integrin-Related Gene Products and ADAM28 as Relevant to B-Cell Acute Lymphoblastic Leukemia (B-ALL).","authors":"Makayla R K Wilkins, Brett E Pickett","doi":"10.3390/cimb47090699","DOIUrl":"10.3390/cimb47090699","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with pediatric ALL having a ~90 percent cure rate, while the adult cure rate is considerably lower. B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of ALL and is generally treated through a variety of chemotherapy drugs that can cause undesired side effects, adverse events, or other complications. Consequently, there is a need for improved understanding of the shared gene expression profiles and underlying molecular mechanisms shared among various B-ALL subtypes. In this study, 259 publicly available RNA-sequencing samples were evaluated and retrieved from the NCBI Gene Expression Omnibus (GEO) database and then pre-processed using a robust computational workflow. Differential gene expression, pathway enrichment, marker prediction, and drug repurposing analyses were then performed to facilitate a better mechanistic understanding of disease. We found both previously identified as well as novel differentially expressed genes. Specifically, we observed upregulation in the <i>HIST2H2AA3</i>, <i>EPHA7</i>, and <i>MPR1</i> genes; while downregulation was observed for the <i>IGHA1</i>, <i>ANGPTL1</i>, and <i>CHAD</i> genes. We identified multiple pathways, including \"Integrins in Angiogenesis\", to be significantly affected in B-ALL. We then used these significant pathways to predict and rank 306 existing therapeutic targets that could potentially be repurposed for B-ALL, including three that have not been evaluated in human clinical trials. Using a tree-based classification algorithm, we also predicted ADAM28 as a possible mechanistic marker. The results of this study have potential implications for patients who have been diagnosed with B-ALL by providing improved mechanistic understanding and information on possible diagnostics and repurposed therapeutics for B-ALL.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Petar Vranjić, Mladen Vuković, Senka Blažetić, Barbara Viljetić
{"title":"Ketogenic Diet and Thyroid Function: A Delicate Metabolic Balancing Act.","authors":"Petar Vranjić, Mladen Vuković, Senka Blažetić, Barbara Viljetić","doi":"10.3390/cimb47090696","DOIUrl":"10.3390/cimb47090696","url":null,"abstract":"<p><p>The ketogenic diet (KD), a high-fat, low-carbohydrate diet, causes profound metabolic adaptations that go beyond energy production and affect endocrine function and thyroid hormone regulation. By shifting the body's primary fuel source from glucose to fatty acids and ketones, the KD alters insulin signaling, inflammation levels and deiodinase activity, which together affect thyroid hormone metabolism. While this metabolic shift offers potential benefits such as improved insulin sensitivity and reduced systemic inflammation, it also raises concerns about reduced triiodothyronine (T3) levels and altered hypothalamic-pituitary-thyroid (HPT) axis dynamics. This review explores the mechanisms by which the KD affects thyroid function, highlighting both the potential therapeutic benefits and associated risks. Special attention is given to how genetic predispositions, gut microbiota composition and sex-based hormonal differences influence thyroid adaptation to a KD. In addition, there are indications that the influence of the KD on cell metabolism could have therapeutic potential in conditions such as autoimmune thyroid diseases and thyroid cancer. Understanding the delicate balance between the benefits and risks of KD for thyroid health is essential for optimizing its clinical applications and defining individual nutritional strategies.</p>","PeriodicalId":10839,"journal":{"name":"Current Issues in Molecular Biology","volume":"47 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}